Neovascularization is deeply involved in the onset and progress of various kinds of inflammatory diseases such as rheumatoid arthritis and psoriasis; ocular diseases such as diabetic retinopathy, retinopathy of prematurity, senile macular degeneration, retinal vein occlusion, retrolental fibroplasia, neovascularization associated with keratoplasty, glaucoma, and ocular tumors; and various kinds of tumors. In particular, it is known that neovascularization or invasion of vessels is observed in the corneas of patients with Stevens-Johnson syndrome and similar diseases; ocular pemphigoid and similar diseases; corneal chemical injuries caused by various kinds of agents having cytotoxicity, for example, alkaline, acid, detergents, various kinds of solvents, and volatile gases; trachoma; viral infections; phlyctenular keratitis; keratoplasty; and patients who use contact lenses for long periods. Aqueous chambers, lenses, and vitreous are originally transparent without vessels, and if neovascularization occurs in these tissues, severe visual loss occurs, resulting in difficulties in everyday life. Therefore, agents which inhibit neovascularization have recently been considered for development as preventive or therapeutic agents for the above-mentioned diseases.
Examples of such angiogenesis inhibitors reported up to the present are as follows: protamine application (Taylor, S. et al., Nature, 297, 307, 1982), a combination of heparin and cortisone (Folkman, J. et al., Science, 221, 71, 1983), prednisolpne-acetate (Robin, J. B., Arch. Opthalmol., 103, 284, 1985), sulfonated polysaccharide (Japanese Patent Laid-Open No. 63-119500), Herbimycin A (Japanese Patent Laid-Open No. 63-295509), Fumagillin (Japanese Patent Laid-Open No. 1-279828). However, these angiogenesis inhibitors are unsatisfactory as preventive or therapeutic agents because of insufficient activity and side effects, such as toxicity; thus, useful agents in inhibiting neovascularization have been expected. Particularly in the ocular field where it is necessary to use medicines while maintaining ongoing visual functions, the development of safe medicines which have no adverse effects on other ocular tissues has been awaited.
Concerning interferon .alpha., the therapeutic possibly for ocular diseases accompanied with neovascularization is suggested in cases of age-related macular degeneration (Fung, W. E. Am. J. Ophthalmol., 112, 349 1991), neovascular glaucoma (Miller, J. W. et al. Ophthalmolography, 100, 9 1992), and diabetic retinopathy (Wakelee-Lynch, J. and Banks, P., Diabetes Care, 15, 300, 1992), though the practical usefulness is still unknown.
An object of the present invention is to provide an useful corneal angiogenesis inhibitor.